Pump Cassette With Spiking Assembly

ABSTRACT

An apparatus for use in a fluid processing system having a pump. The apparatus includes a pump cassette for use with the pump. The pump cassette includes at least one pump chamber and a first port in selective fluid communication with the at least one pump chamber. A spiking assembly includes at least one hollow spike having a piercing end for piercing a first container. The at least one hollow spike includes a first spike in fluid communication with the first port of the pump cassette.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a divisional of co-pending U.S. application Ser. No.10/697,862 filed on Oct. 30, 2003, herein incorporated by reference.

The present application also may include subject matter related to oneor more of the following commonly-owned United States patentapplications, each of which was filed on even date herewith and ishereby incorporated herein by reference in its entirety:

U.S. patent application Ser. No. 10/696,969 entitled SYSTEM, DEVICE, ANDMETHOD FOR MIXING A SUBSTANCE WITH A LIQUID (referred to herein as“Application D70”);

U.S. patent application Ser. No. 10/696,893 entitled SYSTEM, DEVICE, ANDMETHOD FOR MIXING LIQUIDS (referred to herein as “Application D7 I”);

U.S. patent application Ser. No. 10/696,818 entitled TWO-STAGE MIXINGSYSTEM, APPARATUS, AND METHOD (referred to herein as “Application D72”);

U.S. patent application Ser. No. 10/697,176 entitled SYSTEM AND METHODFOR PUMPING FLUID USING A PUMP CASSETTE (referred to herein as“Application D73”);

U.S. patent application Ser. No. 10/696,984 entitled DOOR LOCKINGMECHANISM (referred to herein as “Application D74”);

U.S. patent application Ser. No. 10/697,450 entitled BEZEL ASSEMBLY FORPNEUMATIC CONTROL (referred to herein as “Application D75”); and

U.S. patent application Ser. No. 10/696,990 entitled PUMP CASSETTE BANK(referred to herein as “Application D85”).

FIELD OF THE INVENTION

The present invention relates generally to pumping liquids, and moreparticularly to a pump cassette and spiking assembly for use in a fluidprocessing system.

BACKGROUND OF THE INVENTION

Millions of people receive blood transfusions each year. Althoughhelpful in many cases, blood transfusions have associated risks. Amongothers, there is a risk that microorganisms capable of causing disease(i.e., pathogens) could pass from the donor blood to the ultimate bloodrecipient. For example, untreated blood used in a blood transfusioncould have pathogens causing the West Nile Virus, or AIDS. It thus iscritical for the public health to ensure that transfused blood issubstantially free of pathogens.

The medical community has responded to this need by developing varioustechniques for removing known and unknown pathogens from donated blood.One technique involves mixing precise amounts of a diluted anti-pathogencompound with blood. Some time after mixing, a rinsing process removesthe anti-pathogen compound from the blood. One complexity with thisprocess, however, is the fact that the diluted anti-pathogen compoundhas a very short shelf life (e.g., on the order of about four hours).Accordingly, the diluted anti-pathogen compound must be produced arelatively short time before it is mixed with blood.

The anti-pathogen compound is not easy to handle before it is diluted.To the contrary, it has a very high pH (e.g., on the order of 11.0 orhigher) and thus, is highly caustic and toxic. Mere contact with theundiluted solution can melt plastic, or burn flesh. Because of theseundesirable properties, the undiluted solution typically is manuallydiluted by highly trained laboratory technicians that necessarily mustbe protected from direct contact with it. Consequently, laboratorytechnicians often are required to wear relatively impermeable protectivegear while diluting the solution behind a chemical laminar flowhood.Such a process, however, is inherently slow, imprecise, and costly dueto the multitude of safety requirements. Moreover, even with safeguards,diluting the undiluted solution still poses a risk to the laboratorytechnician.

SUMMARY OF THE INVENTION

In connection with developing a mixing system for treating blood withdiluted anti-pathogen, a new apparatus for use in a fluid processingsystem having a pump was invented. In accordance with one aspect of theinvention, the apparatus includes a pump cassette for use with the pump.The pump cassette includes at least one pump chamber and a first port inselective fluid communication with the at least one pump chamber. Aspiking assembly includes at least one hollow spike having a piercingend for piercing a first container. The at least one hollow spikeincludes a first spike in fluid communication with the first port of thepump cassette.

In accordance with related embodiments of the invention, first tubingmay be coupled at one end to the first port of the pump cassette and atanother end to a non-piercing end of the first spike so as to provide afirst fluid path between the first port and the first spike. The firstport may be a fluid outlet port, wherein the first spike provides afluid inlet to the first container. Alternatively, the first port may bea fluid inlet port, wherein the first spike provides a fluid outlet fromthe first container.

In accordance with further related embodiments of the invention, thespiking assembly includes a housing. The housing may include twosubstantially identical halves that are joined together. The spikingassembly may further includes a spike holder captured by the housing,the spike holder engaging the at least one spike. The spike holder maybe overmolded onto the at least one spike. The overmolded spike holdermay include, for each spike, a tubing barb proximate to the non-piercingend of the spike for coupling a tube to the spike. The housing mayinclude at least one element for engaging each tube about the tubingbarb so as to secure the tubes within the housing. The spiking assemblymay include a spike guard disposed within the housing and overlaying thepiercing end of the at least one spike. The spike guard may include agrommet capable of being pierced by the at least one spike, and that mayfunction as a fluid seal when in contact with the first container. Thespike guard may include at least one tab for engaging one or more slotsin the housing to prevent movement of the spike guard, the at least onetab capable of being disengaged from the one or more slots to allowmovement of the spike guard towards the at least one spike such that theat least one spike can pierce the grommet. The housing may include atleast one element for engaging a container holder. The at least oneelement may include a surface forming an undercut for engaging at leastone corresponding feature on the container holder.

In accordance with still further related embodiments of the invention,the at least one spike includes a second spike. Second tubing may becoupled at one end to a non-piercing end of the second spike, and atanother end to a second container, so as to provide a second fluid pathbetween the second spike and the second container. A filter may becoupled between the second spike and the fluid receptacle along thesecond fluid path.

In accordance with other related embodiments of the invention, the pumpcassette may include a second port in selective fluid communication withthe at least one pump chamber. Third tubing may be coupled at one end tothe second port, the third tubing providing a third fluid path betweenthe second port and a third container. A third spike may be coupled toanother end of the third tubing for piercing the third container. The atleast one pump chamber may includes two pump chambers, wherein fluid canbe pumped from one port into one pump chamber while fluid is pumped fromthe other pump chamber out the other port. The pump cassette may bepneumatically controlled by the pump.

In accordance with another aspect of the invention, an apparatus forpiercing a container includes a housing. A spike holder is captured bythe housing. The spike holder engages at least one hollow spike having apiercing end for piercing the container. A spike guard is disposedwithin the housing and overlays the piercing end of the at least onespike.

In accordance with related embodiments of the invention, the spike guardmay include a grommet capable of being pierced by the at least onespike. The grommet may function as a fluid seal when in contact with thecontainer. The at least one hollow spike includes a first spike forproviding a fluid inlet to the container. The housing may include twosubstantially identical halves that are joined together. The spikeholder may be overmolded onto the at least one spike. The overmoldedspike holder may include, for each spike, a tubing barb proximate to thenon-piercing end of the spike for coupling a tube to the spike. Thehousing may include at least one element for engaging each tube aboutthe tubing barb so as to secure the tubes within the housing. The spikeguard may include at least one tab for engaging one or more slots in thehousing to prevent movement of the spike guard, the at least one tabcapable of being disengaged from the one or more slots to allow movementof the spike guard towards the at least one spike such that the at leastone spike can pierce the grommet. The housing may include at least oneelement for engaging a container holder. The at least one element mayinclude a surface forming an undercut for engaging at least onecorresponding feature on the container holder. The at least one spikemay include a second spike for providing an outlet from the container.

In accordance with another aspect of the invention, a kit includes apump cassette for use with a pump. The pump cassette includes at leastone pump chamber and a first port in selective fluid communication withthe at least one pump chamber. The kit further includes a spikingassembly that includes at least one hollow spike having a piercing endfor piercing a first container. First tubing is also provided in the kitfor connecting at one end to the fluid outlet port of the pump cassetteand at another end to a non-piercing end of a first spike for providinga first fluid path between the first port and the first spike.

In accordance with related embodiments of the invention, the at leastone spike further includes a second spike. The kit may further include asecond container and second tubing. One end of the second tubing may beconnected to a non-piercing end of the second spike, while another endmay be connected to the second container for providing a second fluidpath between the second spike and the second container. A filter may beprovided that can be connected between the second spike and the secondcontainer along the second fluid path. The kit may further include thirdtubing, which can be connected at one end to a fluid inlet port of thepump cassette. A third spike may be coupled to another end of the thirdtubing for piercing a third container.

In accordance with still another aspect of the invention, a method forattaching tubing to one or more spikes of a spiking assembly ispresented. The method includes overmolding a spike holder over a portionof each of the spikes such that each spike maintains a substantiallyfixed position within the spike holder and at least one barb is formedproximate to each spike. A tube is attached to each spike, each tubeinstalled over one of the barbs.

In accordance with related embodiments of the invention, the tubing maybe captured within a housing. The housing includes at least one elementfor engaging the tubing about the barbs so as to secure the tubes withinthe housing.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings:

FIG. 1A shows an exemplary blood processing system 100 having acompounder in accordance with an embodiment of the present invention;

FIG. 1B shows an exemplary wiring diagram for one embodiment of theblood processing system shown in FIG. 1A;

FIG. 1C shows an exemplary wiring diagram for another embodiment of theblood processing system shown in FIG. 1A;

FIG. 2A shows an exemplary vial assembly in accordance with anembodiment of the present invention;

FIG. 2B shows a perspective view of the vial receptacle in accordancewith an embodiment of the present invention;

FIG. 3A shows an exemplary compounder disposable set in accordance withan embodiment of the present invention;

FIG. 3B shows a front view of the compounder pump cassette in accordancewith an embodiment of the present invention;

FIG. 3C shows a rear view of the compounder pump cassette in accordancewith an embodiment of the present invention;

FIG. 3D shows a cross-sectional view of the spike receptacle inaccordance with an embodiment of the present invention;

FIG. 3E shows a side view of a spike receptacle housing section inaccordance with an embodiment of the present invention;

FIG. 3F shows a top view of a spike receptacle guard in accordance withan embodiment of the present invention;

FIG. 3G shows an exploded perspective view of the spike receptacle inaccordance with an embodiment of the present invention;

FIG. 3H shows a cut-out perspective view of the spike receptacle inaccordance with an embodiment of the present invention;

FIG. 3I shows a cross-sectional view of an exemplary spike having twofluid channels in accordance with an embodiment of the presentinvention;

FIG. 4 shows a conceptual block diagram of the compounder in accordancewith an embodiment of the present invention;

FIG. 5A is an architectural flow diagram showing the relationshipbetween the pneumatic control assembly and the other assemblies inaccordance with an embodiment 5 of the present invention;

FIG. 5B shows an exemplary embodiment of the pneumatic control assemblyin accordance with an embodiment of the present invention;

FIG. 5C shows an exemplary embodiment of the air pump in accordance withan embodiment of the present invention;

FIG. 6 shows an exploded view of an exemplary front plate assembly inaccordance with an embodiment of the present invention;

FIG. 7A shows an exploded view of the door assembly in accordance withan embodiment of the present invention;

FIG. 7B shows a front perspective view of the door assembly shown inFIG. 7A in accordance with an embodiment of the present invention;

FIG. 7C shows a rear perspective view of the door assembly shown in FIG.7A in accordance with an embodiment of the present invention, in whichthe cassette receptacle is in a retracted position;

FIG. 7D shows a rear perspective view of the door assembly shown in FIG.7A in accordance with an embodiment of the present invention, in whichthe cassette receptacle is in an open position;

FIG. 8A shows a cross-sectional view of an occluder assembly inaccordance with an embodiment of the present invention;

FIG. 8B shows a side perspective view of the occluder assembly shown inFIG. 258A in accordance with an embodiment of the present invention;

FIG. 8C shows an exploded view of the occluder assembly shown in FIG. 8Ain accordance with an embodiment of the present invention;

FIG. 9A shows an exemplary vial spike assembly in accordance with anembodiment of the present invention;

FIG. 9B is a schematic diagram showing the vial spike assembly shown inFIG. 9A prepared for insertion of the vial assembly and the spikereceptacle in accordance with an embodiment of the present invention;

FIG. 9C is a schematic diagram showing the vial spike assembly shown inFIG. 59A with the vial assembly and spike receptacle inserted into thecylinder and the cover in an open position in accordance with anembodiment of the present invention;

FIG. 9D is a schematic diagram showing the vial spike assembly shown inFIG. 9A with the vial assembly and spike receptacle inserted into thecylinder and the cover in a closed position in accordance with anembodiment of the present invention;

FIG. 9E shows a cross-sectional view of the vial spike assembly with thevial assembly and spike receptacle locked and loaded and ready forspiking, in accordance with an embodiment of the present invention;

FIG. 9F shows a cross-sectional view of the vial spike assembly afterspiking is completed, in accordance with an embodiment of the presentinvention;

FIG. 10 shows an exploded view of the vial spike assembly shown in FIG.9A in accordance with an embodiment of the present invention;

FIG. 11 shows an exemplary spiking mechanism in which the vial isinverted and the spikes enter the vial from below, in accordance with analternative embodiment of the present invention;

FIG. 12 shows a process flow diagram describing the compounding andblood treatment process in accordance with an embodiment of the presentinvention;

FIGS. 13A-B show a process flow diagram showing additional details ofthe compounding process shown in FIG. 12 in accordance with anembodiment of the present invention;

FIG. 14 shows a process flow diagram describing the compounder dry CITprocess shown in FIGS. 12 and 13 in accordance with an embodiment of thepresent invention;

FIG. 15 shows a process flow diagram describing the compounder buffersolution priming process shown in FIGS. 12 and 13 in accordance with anembodiment of the present invention;

FIG. 16 shows a process flow diagram describing the compounder wet CITprocess shown in FIGS. 12 and 13 in accordance with an embodiment of thepresent invention;

FIG. 17 shows a process flow diagram describing the process for manualcompounder teardown in accordance with an embodiment of the presentinvention;

FIG. 18 shows a process flow diagram describing the compoundervolumetric calibration process in accordance with an embodiment of thepresent invention; and

FIG. 19 shows a logic flow diagram showing exemplary logic for mixing asubstance with a liquid in accordance with an embodiment of the presentinvention.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Embodiments of the present invention provide for safely and efficientlymixing a substance with a liquid. For convenience, this mixing processmay be referred to hereinafter as “compounding,” and an apparatus thatperforms such compounding may be referred to hereinafter as a“compounder” or “compounder pump.”

In certain embodiments of the present invention, the substance iscontained in a container assembly having a sealed container thatcontains the substance. The container assembly is joined with a portassembly within a receiving chamber. The port assembly provides at leastan inlet to the container, and typically also an outlet from thecontainer, preferably using one or more hollow spikes that pierce acover of the container. The inlet of the port assembly is preferably influid communication with an outlet of a pump cassette. The pump cassetteis preferably controlled pneumatically to pump a liquid to the containerthrough the inlet to produce a solution of substance and liquid.Continued pumping of liquid to the container through the inlet may causethe solution to flow out of the container through the outlet. The outletof the port assembly is preferably in fluid communication with areceptacle to collect the solution flowing from the container.

FIG. 19 is a logic flow diagram showing exemplary logic 1900 for mixinga substance with a liquid in accordance with an embodiment of thepresent invention. Beginning in block 1902, a container having asubstance contained therein is provided, in block 1904. A predeterminedquantity of a liquid is added to the container to produce a solution, inblock 1906. The solution is permitted to flow from an outlet of thecontainer to a receptacle when the solution rises within the containerto a level of the outlet, in block 1908. Typically, liquid continues tobe added to the container so that the resulting solution in thereceptacle reaches has a predetermined concentration of substance toliquid. The logic ends in block 1999.

In certain embodiments of the present invention, the substance is acaustic substance that is provided in a primary container having abottom and a top, with the caustic substance filling the primarycontainer from the bottom to a given point between the bottom and thetop. An outlet is provided in the primary container, such that theoutlet is between the given point and the top. A predetermined amount ofliquid is added to the primary container to produce a combined causticsubstance and liquid solution that rises at least to the level of theoutlet. At least some of the solution is permitted to flow from theprimary container through the outlet after the solution rises to theoutlet.

In exemplary embodiments of the present invention, the substance to bemixed with the liquid is a caustic anti-pathogen compound known asPEN110™ or INACTINE™, which is an organic solvent with a pH over 11 thatis distributed by V.I. Technologies, Inc. of Watertown, Mass. Such ananti-pathogen compound can be used to reduce pathogens in a substancesuch as blood. One problem with such an anti-pathogen compound is thatit typically cannot be added directly to the blood (or other substance)targeted for pathogen reduction. Therefore, the anti-pathogen compoundis preferably mixed with a buffer solution, such as sodium phosphate, toform a working solution that then can be added to the blood or othersubstance to reduce pathogens in the blood. Because of the causticnature of the anti-pathogen compound, the anti-pathogen compound shouldnot come into contact with certain materials, such as plastic tubingcommonly used to carry fluids in pump mechanisms. Therefore, inexemplary embodiments of the present invention, mixing is preferablyaccomplished by pumping the buffer solution into an anti-pathogencompound container through an inlet in order to form a partially dilutedsolution of anti-pathogen compound and buffer solution. The continuedingress of buffer solution to the anti-pathogen compound containerthrough the inlet causes further dilution and also causes the partiallydiluted solution to flow out of the anti-pathogen compound containerthrough an outlet to a working solution container. By partially dilutingthe anti-pathogen compound within the anti-pathogen compound container,the undiluted anti-pathogen compound does not come into contact withanything outside of the anti-pathogen compound container, includinghuman operators, the pump mechanism (including tubing from theanti-pathogen compound container to the working solution container), andthe external environment in general. The anti-pathogen compound istypically diluted to a predetermined concentration (e.g., 1 partanti-pathogen compound to 99 parts buffer solution), withinpredetermined tolerances. The anti-pathogen compound container ispreferably sealed following dilution to allow for safe disposal of theanti-pathogen compound container.

System Overview

FIG. 1A shows an exemplary blood processing system 100 having acompounder in accordance with an embodiment of the present invention.Among other things, the blood processing system 100 includes a singlecompounder pump 102 and ten essentially identical blood pumps 104organized as two banks of five blood pumps each. The compounder pump 102pumps buffer solution from a buffer solution container 110 into a vialof anti-pathogen compound 108. The mixture, referred to as a workingsolution, is pumped into a working solution container 112. Each of theblood pumps 104 mixes working solution from the working solutioncontainer 112 with red blood cell concentrate (RBCC) 106 to form anincubation solution that is pumped into an incubation bag 118. Theincubation solution is typically allowed to incubate for some period oftime, after which it is rinsed to remove the anti-pathogen compound toproduce a pathogen reduced blood product. The blood processing system100 typically also includes two sterile docks 114 that are used by theoperator to splice together plastic tubing as necessary for variousblood processing operations. The blood processing system 100 iscontrolled through a user interface 116.

FIG. 1B shows an exemplary wiring diagram for one embodiment of theblood processing system 100. The compounder pump 102 and the blood pumps104 are typically powered from a common 12-Volt external power supply126, and are controlled by an external process controller 120. Theprocess controller 120 includes the user interface 116, a computer 122,and a serial port concentrator 124. The compounder pump 102 and theblood pumps 104 are in communication with the process controller 120through the serial port concentrator 124, for example, over RS-232communication links. The blood processing system 100 typically includesa tubing sealer 130 for sealing plastic tubing as necessary for variousblood processing operations. The blood processing system 100 typicallyincludes an uninterruptible power supply (UPS) 128 for maintainingelectrical power to the 12-Volt power supply, the process controller,and other components in the event of a primary power loss.

FIG. 1C shows an exemplary wiring diagram for another embodiment of theblood processing system 100. The blood processing system 100 may includea printer in communication with the process controller for printing outreports. The blood processing system 100 may include a card reader 134in communication with the process controller for card-based operatoridentification. The blood processing system 100 may include a wirelessbar code scanner base station 138 in communication with the processcontroller for receiving bar code information scanned using a wirelessbar code scanner 136. Bar codes are typically used to track the varioussolution containers and the pumps on which those containers wereprocessed.

The process controller 120 coordinates the actions of the compounderpump 102, the blood pumps 104, and the operator throughout the variousmixing operations. The process controller 120 initiates high levelembedded commands within the pumps to move and mix the fluids. Theprocess controller 120 instructs the operator through the setup andteardown of each process through the user interface 116. The userinterface 116 is also used to inform the operator of any anomalies thatmay occur during mixing operations.

When the blood processing system 100 is operating from theuninterruptible power supply 128 and at other appropriate times, theprocess controller 120 will prevent compounding and other pumpoperations from starting, although the pumps will generally be allowedto complete any ongoing operations. Furthermore, if the processcontroller fails, the pumps have internal logic for safely completing orterminating any ongoing operations.

Vial Assembly

The anti-pathogen compound is typically provided as a container assemblyincluding a sealed anti-pathogen compound container (typically a sealedglass vial partially filled with anti-pathogen compound) within aprotective holder. The protective holder is designed to prevent breakageof the sealed anti-pathogen compound container in case the containerassembly is dropped or otherwise mishandled, within predeterminedlimits. For convenience, the anti-pathogen compound container may bereferred to hereinafter a “vial,” the protective holder may be referredto hereinafter as a “vial receptacle,” and the container assembly may bereferred to hereinafter as a “vial assembly.”

FIG. 2A shows an exemplary vial assembly 200 in accordance with anembodiment of the present invention. The vial assembly 200 includes avial 210 within a vial receptacle 206. The vial 210 is sealed with apolypropylene screw-on vial cap 208 including a Teflon-faced siliconeseptum 202 that is capable of being pierced by the spikes of a spikereceptacle, as discussed below. The vial receptacle 206 includes a vialcontainment rib 212 for holding the vial 210 within the vial receptacle206. The vial receptacle 206 also includes one or more rows of spikereceptacle engagement teeth 204 that are undercut for engaging acorresponding vial receptacle locking feature on the spike receptacle sothat the spike receptacle cannot be easily removed from the vialreceptacle 206 after the vial 210 is spiked, as discussed below.Multiple rows of spike receptacle engagement teeth 204 are typicallyincluded to accommodate vial height tolerances so that spiking andlocking can be accomplished with various vial heights. The vialreceptacle 206 also includes switch engagement features 214 that areessentially protruding rings that operate various switches in a spikingcylinder, as discussed below.

FIG. 2B shows a perspective view of the vial receptacle 206 inaccordance with an embodiment of the present invention. The top portionof the vial receptacle 206 incorporating the spike receptacle engagementteeth 204 is preferably divided into four tabs 220, 222, 224, and 226.The tabs are able to deflect inward during spiking so as to facilitateengagement with the vial receptacle locking feature on the spikereceptacle, as discussed below. Each tab includes multiple rows of spikereceptacle engagement teeth. The teeth on each pair of opposing tabs areessentially aligned, although the teeth on adjacent pairs of tabs arestaggered by approximately half the height of a tooth. Among otherthings, this staggering of the spike receptacle engagement teeth 204provides twice the number of engagement locations without having toreduce the size of the teeth.

Compounder Disposables

In order to create the inlet and outlet for diluting the anti-pathogencompound in the vial 210 as discussed above, the septum 202 ispreferably pierced by a port assembly having two hollow spikes, oneacting as the inlet and the other acting as the outlet. For convenience,this piercing operation may be referred to hereinafter as “spiking,” andthe port assembly may be referred to hereinafter as a “spikereceptacle.” The outlet spike is connected through plastic tubing to theworking solution container. The inlet spike is connected through plastictubing to the output port of a pump cassette. The pump cassette also hasan inlet port that can be connected through plastic tubing to a buffersolution container. The pump cassette is installed in the compounder andserves as an interface between the compounder, the vial 210, and thebuffer solution container for pumping buffer solution from the buffersolution container to the vial 210, as discussed below.

In order to dilute the anti-pathogen compound, the buffer solution istypically drawn from the buffer solution container through the inletport into a chamber of the pump cassette and is then pumped from thepump cassette chamber through the outlet port to the inlet spike andinto the vial. Alternatively, fluid can be pumped out of the vial intothe cassette, and further pumped into a container for mixing withanother fluid. In exemplary embodiments of the present invention, thespiking operation and the pumping operations (including drawing thebuffer solution from the buffer solution container and pumping thebuffer solution to the inlet spike) are controlled pneumatically, asdiscussed below.

In a typical embodiment of the present invention, the pump cassette, thespike receptacle, the working solution container, and various plastictubes connected thereto form a compounder disposable set. The compounderdisposable set is used for a single compounding operation and is thendiscarded.

FIG. 3A shows an exemplary compounder disposable set 300 in accordancewith an embodiment of the present invention. The compounder disposableset 300 includes a pump cassette 306 including an inlet port 305, andoutlet-port 308, and a vent 307. The inlet port 305 is connected to oneend of a plastic tube 304 having, on its other end, a buffer bag spike302 for piercing a buffer solution container. The outlet port 308 isconnected to one end of a plastic tube 309, the other end of which isconnected to an inlet spike 312 of a spike receptacle 310. An outletspike 314 of the spike receptacle 310 is connected to a tube 318 thatleads through a filter 320 to a working solution container 322. A tubingclamp 316 is used to crimp the tubes 309 and 316 near the spikereceptacle 310 after the compounding operation is complete.

FIG. 3B shows a front view of the compounder pump cassette 306 ingreater detail. The pump cassette 306 is essentially a rigid coreincluding formations and sealing ribs 340 constituting various pumpingchambers, fluid valves, and fluid pathways (channels). The rigid core iscovered on each side by a flexible membrane. The flexible membranes sealagainst the core and isolate the compounder pump 102 from fluids withinthe cassette. The pump cassette 306 is designed to interface with thecompounder pump 102 in only one direction. For example, the pumpcassette 306 typically includes an asymmetric feature (such as theplacement of tubing) that prevents the compounder door from closing ifthe pump cassette 306 is inserted incorrectly.

The pump cassette 306 includes the outlet port 308, the vent port 307,and the inlet port 305. The pump cassette 306 also includes two pumpingchambers 333 and 334 that are used to draw buffer solution from thebuffer solution container through the inlet port 305 and pump the buffersolution to the vial 210 through the outlet port 308.

FIG. 3C shows a rear view of the compounder pump cassette 306. Inaddition to the inlet port 305, the vent port 307, the outlet port 308,and the pump chambers 333 and 334, the pump cassette 306 includesvarious “volcano” valves 324, 326, 328, 330, 332, 336, and 338 that areused to open and close various fluid pathways within the pump cassette306. The volcano valves and the pumping chambers are preferably operatedpneumatically from the rear side of the pump cassette 306, as discussedbelow. The valve 324 is used to control pumping through the vent port,for example, to allow air to be pumped from the pump chambers 333 and334 out the vent port 307. The valves 326 and 332 are used for primingthe pump chambers 334 and 333, respectively. The valves 328 and 336 areused to control pumping of buffer solution through the inlet port 305into the pump chambers 334 and 333, respectively. The valves 330 and 338are used to control pumping of buffer solution through the outlet port308 from the pump chambers 334 and 333, respectively.

FIG. 3D shows a cross-sectional view of the spike receptacle 310 ingreater detail. The spike receptacle 310 includes a housing 344 thatholds spikes 354 and a guard 360, and is designed to mate with the vialreceptacle 206 during spiking, as discussed below. The housing 344 ispreferably made up of two identical halves that, when joined together,are held together by ribs on each side that align with and are engagedby slots on the other side.

The spikes 354 are contained by a polycarbonate spike holder 352 that ispreferably overmolded onto the two spikes 354. The overmolded spikeholder 352 includes tubing barbs 342. Tubing is attached to the spikesover the tubing barbs 342. The overmolded spike holder 352 helpsmaintain parallelism of the spikes 354, and provides a fluid-tightconnection with the tubing.

The top portion of the housing 344 has an area that engages theovermold's barb feature so as to capture the tubing within the housing344. This creates a double-mechanical (as well as bonded) feature thatpermanently attaches the tubing to the spike. The spike housing 344 alsofeatures an undercut vial receptacle locking feature 348 that engagesthe spike receptacle engagement teeth 204 of the vial receptacle 206 topermanently attach the spike receptacle 310 to the vial receptacle 206after spiking, as discussed below. The spike housing 344 also includes arim 398 that is slightly wider than the remainder of the housing 344.The rim 398 prevents the spike receptacle 310 from being fully insertedinto the vial spike assembly 406. The rim 398 includes two orientationtabs 399 that are used to align the spike receptacle 310 within the vialspike assembly 406.

The guard 360 protects the spikes 354 and protects the operator from thespikes 354. The guard 360 includes a center hole that is filled orcovered with an elastomeric (silicone) grommet 356. The guard 360 isdesigned to engage the vial cap 208, and has four release tabs 358 thathold it loosely in the housing 344. The release tabs 358 protrude outthrough slots in the housing 344, making it difficult to move the guard360 when the tabs 358 are in place. When the assembly is placed into thevial spiking assembly, the fingers are pushed in by the inner wall ofthe spiking cylinder, releasing the guard 360 so that spiking can occurthrough the grommet 356, as discussed below. The grommet 356 also actsas a redundant seal between the vial cap 208 and the spike guard 360 incase fluid were to leak through the septum 202 around the spikes 354during pumping.

The spike receptacle 310 includes a sensor feature 346 that isessentially a protruding ring near the top of the spike receptacle 310.The sensor feature 346 is designed to engage a switch in a lockingmechanism of the vial spiking assembly, as discussed below.

FIG. 3E shows a side view of a spike receptacle housing section 344 inaccordance with an embodiment of the present invention. Among otherthings, the housing section 344 includes the rim 398, which preferablyextends around the outer periphery of the housing section 344, and theundercut vial receptacle locking feature 348, which preferably extendsaround the inner periphery of the housing section 344. The housingsection 344 includes a center channel 397 with a slot 396 for engaging atab 358 of the guard 360, and also includes a partial channel 395 with apartial slot 394 at each edge such that, when two housing sections 344are joined, four channels with slots are formed (two central and twowhere the housing sections meet. When the guard tabs are positionedwithin the slots, the guard 360 is held substantially in place so as tocover the spikes. When the guard tabs are released from the slots duringspiking, the guard 360 is able to slide upward along the channels toallow spiking to occur, and also to provide a redundant seal against thevial in case fluid leaks from around the spikes. The housing section 344includes formations 393 for receiving and engaging the overmolded spikeholder 352 with attached tubing so as to hold the spikes and associatedtubing in place.

FIG. 3F shows a top view of the guard 360 in accordance with anembodiment of the present invention. The guard 360 includes four tabs358 that are positioned within, and are engaged by, the channels andslots in the housing 344. The tabs 358 are pushed inward during spikingin order to release the tabs from the slots in the housing 344. FIG. 3Gshows an exploded perspective view of the spike receptacle 310 inaccordance with an embodiment of the present invention. The spikereceptacle 310 includes two housing sections 344, guard 360, grommet356, spikes 354 with overmolded spike holder 352, and associated tubing.The tubing is pushed onto the overmolded spike holder 352 over thebarbs. The grommet 356 is inserted into a hole in the guard 360 suchthat it is held in place by the guard 360 and covers the hole in theguard 360. As shown in FIG. 3H, the overmolded spike holder 352 withattached tubing fits into corresponding formations of the housingsections 344, and the tabs of the guard 360 fit into the slots in thehousing sections 344.

With reference again to FIG. 2B, during spiking, the spike receptacle310 and the vial receptacle 206 are forced together such that the spikereceptacle 310 becomes locked onto the vial receptacle 206 over the tabs220, 222, 224, and 226. During spiking, the tabs deflect inward asneeded to allow the vial receptacle locking feature 348 to pass oversuccessive rows of spike receptacle engagement teeth 204 until the vialreceptacle 206 is seated as far onto the vial receptacle 206 aspossible. The staggered teeth provide twice as many engagement pointsfor the vial receptacle locking feature 348 compared to teeth that arenot staggered.

While the spiking receptacle 310 preferably includes two hollow spikesfor forming the inlet and outlet, it should be noted that the presentinvention is in no way limited to two spikes. A single spike having bothan inlet channel and an outlet channel could be used. Alternatively,multiple inlet spikes and/or multiple outlet spikes could be used.

FIG. 3I shows a cross-sectional view of an exemplary spike having twofluid channels 381 and 382 in accordance with an embodiment of thepresent invention. In a typical embodiment of the invention, one of thefluid channels would be used to provide an inlet to the vial, while theother fluid channel would be used to provide an outlet from the vial.Appropriate tubing connections would typically be provided to allowseparate tubing to be connected to the two fluid channels.

Compounder

As discussed above, the compounder 102 creates a working solution ofanti-pathogen compound and buffer solution. A disposable pump cassette306 serves as an interface between the compounder 102, the vial 210, thebuffer solution container, and the working solution container, so thatno anti-pathogen compound, buffer solution, or working solution comesinto actual contact with the components of the compounder 102. Thecompounder 102 preferably uses pneumatics to operate the pump cassette306 as well as other components, as discussed below. Each compoundingcycle of the compounder 102 typically makes a sufficient quantity ofworking solution for processing 30 RBCC containers by the ten bloodpumps 104.

The compounder produces the working solution by pumping a quantity ofbuffer solution from the buffer solution container to the vial so as tomix with the anti-pathogen compound in the vial to produce workingsolution. Adding the buffer solution to the vial causes the level of theworking solution to rise within the vial. When the working solutionrises to the level of an outlet provided in the vial, the workingsolution is permitted to flow from the vial to the working solutioncontainer.

The compounder 102 preferably includes a library of generic pump control(N-Pump) functions. The N-Pump library functions are used to performvarious generic pumping operations such as, for example, pumping fluidinto a chamber of the pump cassette, pumping fluid out of a chamber ofthe pump cassette, measuring the amount of fluid pumped, performing airdetection, and maintaining tank pressures. The compounder 102 preferablyalso includes a Fluid Logic Module (FLM) that contains higher levelfunctions that employ the N-Pump library functions to implementcompounder-specific functions (such as specific logic for mixing thebuffer solution with the anti-pathogen compound to produce the workingsolution).

The compounder 102 includes one master board connected to two pumpboards that together perform the N-Pump and FLM functions. The masterboard communicates to each of the pump boards via a multi-drop RS-485bus. Each pump board controls a single pump chamber of the pump cassette306 and the valves on its board.

In the compounder 102, the pump chambers are synchronized to pump inseries. Thus, as one chamber is filling with buffer solution, the otherchamber will be delivering buffer solution to the vial. The pumpingalgorithm is typically terminated when the volume of buffer solutionpumped is within one pump stroke of the target volume.

FIG. 4 shows a conceptual block diagram of the compounder 102 inaccordance with an embodiment of the present invention. Among otherthings, the compounder 102 includes a door assembly 402, an occluderassembly 404, a vial spike assembly 406, a front plate assembly 408, apneumatic control assembly 410, a power/communication interface 412including connectors for the 12-Volt power supply and the RS-232communication link to the process controller 120, and chassis components414. Each of these assemblies will be discussed below.

Pneumatic Control Assembly

The pneumatic control assembly 410 provides positive and negative airpressure for operating the various other pneumatically controlledcomponents and also acts as the general controller for the compounder102. FIG. 5A is an architectural flow diagram showing the relationshipbetween the pneumatic control assembly 410 and the other assemblies inaccordance with an embodiment of the present invention. In this figure,the pneumatic control assembly 410 is represented by master module 512,accumulator assembly 513, and two buffer pump modules 514 and 515. Theair pump 511 is considered to be one of the chassis components 414. Theair pump 511 generates high and low air pressure for the master module512, which stores high and low air pressure in the accumulator assembly513. The pneumatic control assembly 410 directs air pressure (positiveand negative), from the DC air pump 411, to the various pneumaticmechanisms of the pump. The master module 512 pneumatically controls abladder in the occluder assembly 404, a bladder in the door assembly402, and a bladder in the vial spiking assembly 406, as discussed below.The master module 512 provides high and low air pressure to the bufferpump modules 514 and 515. Each buffer pump module 514 and 515 controls asingle pump chamber of the pump cassette 306 through the front plateassembly 408 and the valves on its module.

FIG. 5B shows an exemplary embodiment of the pneumatic control assembly410 in accordance with an embodiment of the present invention. Amongother things, the pneumatic control assembly 410 includes manifoldmounting bracket 502, a negative pressure accumulator (pressure bottle)513 a, a positive pressure accumulator (pressure bottle) 513 b, a manualdoor vent mechanism 503, the Tank Management Module Assembly 512, thetwo Chamber Module Assemblies 514 and 515, and associated tubing andfittings.

The tank management module 512 includes an input/output (I/O) board, aCPU board, a valve-interface board, a pneumatic manifold system,pneumatic valves, pressure transducers 2-vent covers (mufflers),stand-offs, and associated tubing and fittings. The tank managementmodule 512 is used to control the pressures in the accumulators 513, abladder in the door assembly 402, a bladder in the occluder assembly404, and a bladder in the vial spiking assembly 406. The I/O boardcontains electrical controls for controlling LEDs that provide statusinformation to the operator and for controlling various sensors in thevial spiking assembly 406. The pressure transducers are used to monitorthe pressures of the accumulators 513 and the bladder in the doorassembly 402.

In the un-powered state, the pneumatic valve that controls flow to thebladder in the door assembly 402 preferably shuts closed. This preventsthe door from being opened in the event of a loss of power.

In the un-powered state, the pneumatic valve that controls flow to thebladder in the occluder assembly 404 is preferably channeled to vent.This causes the occluder to occlude the tubing to prevent further flowof fluid through the tubing, as discussed below.

Each chamber module 514 and 515 includes a CPU board, a valve interfaceboard, pneumatic manifold system, pneumatic valves (including a VSO(variable) valve), a VSX chamber (504 and 505 respectively), O-ring,copper mesh, vent cover (muffler), stand-offs, pressure transducers, andassociated tubing and fittings. Each chamber module assembly controlsthe pneumatics for one of the pumping chambers and its associatedvalves. The VSX chambers 504 and 505 act as reference volumes in orderto measure the volume of fluid that is delivered with the FMS system.The pressure transducers are used to monitor the pressure of the VSXchamber, and of the pumping chamber. The positive pneumatic systemcontains a pressure relief valve to prevent the air pump frompressurizing the positive system to greater than 16.0 psig.

In the un-powered state, all of the pneumatic valves preferably open thefluid valves to the positive pressure line, This ensures that the fluidvalves are closed if there is a loss of power.

The compounder 102 typically includes three microprocessor systems, oneon the tank management module 512 and one on each of the chamber modules514 and 515. These three microprocessor systems monitor each other fornormal operation. Each microprocessor system also monitors key internalprocesses and data for validity. If any of these monitors fail, afailsafe line permits any of the three processors to stop pumpingoperations, close all of the fluid valves and occluder, and send ananomaly signal to the process controller. If the compounder 102 detectsan anomaly with the commands received from the process controller (e.g.,commands received out of sequence), then the compounder will stop fluidflow and send an anomaly signal to the process controller.

FIG. 5C shows an exemplary embodiment of the air pump 511 in accordancewith an embodiment of the present invention. The air pump 511 includes apump motor 591 mounted to a pump plate 592 using double-sided tape 594and two miniature nylon cable ties 595. Four ribbed isolator grommets593 are inserted into corresponding openings in the pump plate 592.

Front Plate Assembly

The front plate assembly 408 includes all necessary pneumatic pathwaysto interface to the disposable pump cassette 306. The front plateassembly 408 includes a bezel and a bezel gasket through which the pumpcassette 306 is operated. During operation of the compounder 102, thepump cassette 306 is positioned in the door assembly 402 and is pressedagainst the front plate assembly 408 in alignment with the bezel andbezel gasket by a bladder in the door assembly 402, as discussed below.Air lines connected to the bezel from the pneumatic control assembly 410are used to displace membranes of the bezel gasket to operate thevarious valves and chambers of the pump cassette 306.

FIG. 6 shows an exploded view of an exemplary front plate assembly 408in accordance with an embodiment of the present invention. Among otherthings, the front plate assembly 408 includes a rigid front plate 602 towhich are mounted a bezel 604, chamber foam 606, bezel gasket 612,gasket retainer 614, hardware 616, dowel pins 618, and grommet 620. Thebezel 602 includes two chamber cavities for respectively operating thetwo pump chambers of the pump cassette 306. The bezel 602, chamber foam606, and bezel gasket 612 are mounted to the front plate 602 by thegasket retainer 614 and associated hardware 616. The front plate 602includes holes for allowing air tubes to pass between the rear of thebezel 604 and the pneumatic control assembly 410, which is typicallysituated behind the front plate 602. The front plate 602 also includesopenings for an occluder and for engaging a door latch mechanism.

In exemplary embodiments of the present invention, the bezel is apolycarbonate/ABS component that is molded with rib structures in one ofthe chamber cavities. The bezel with rib structures is used in the bloodpump 104, and is described in greater detail in Application D71 and inApplication D75. The rib structures are removed for use in thecompounder 102.

The pneumatic system's tubing connections are typically accomplishedusing integral ports on the bezel 604, eliminating independent fittingsand accompanying O-rings. The bezel gasket 612 is used in conjunctionwith the bezel 604. The bezel gasket 612 is used to seal the fluid pathsof the pump cassette and to provide an interface to actuate the pumpcassette valves. The tubing is fed through clearance holes in the frontplate 602, so that it can be connected to the pneumatic manifold systemlocated behind the front plate 602. The front plate 602 supports thebezel from behind. The bezel gasket 612 is placed over the bezel 604, onthe front side, and held in place using the gasket retainer 614 (whichalso fastens the bezel 604 to the front plate 602).

Door Assembly

The door assembly 402 provides a means to load and align the disposablecassettes within the compounder 102. The door assembly 402 provides aforce on the disposable cassette against the bezel components of thefront plate assembly 408 in order to provide sealing of the cassette'sfluid paths and valves, as described in greater detail in ApplicationD73. The door assembly 402 includes a special latch system that helpsmaintain the seal, and also helps prevent accidental opening of the doorduring processing, as described in greater detail in Application D74.The door assembly 402 also provides a surface for the occluders tofunction against.

FIG. 7A shows an exploded view of the door assembly 402 in accordancewith an embodiment of the present invention. Among other things, thedoor assembly 402 includes a door cowl 701, a latch spring post 702, adoor latch 703, a cassette receptacle 704, a back plate 705, a latch pin706, a bladder 707 with an attached pneumatic circuit 730, a frame 708,a door pin 709, a door mounting bracket 710, a piston assembly 711including a piston plate 731 and a piston cover 732, a human interfaceboard assembly 712, double coated tape 713, a miniature cable tie 714,recessed bumpers 715, E-rings 722, cable tie mount 723, torsion springs724 and 725, extension spring 726, a cassette orientation tab 799, andvarious screws 716, 717, 718, 719, 720, and 721. The human interfaceboard assembly 712 is mounted to the inside of the door cowl 701. Thepneumatic interface plate 707, double coated tape 713, and pistonassembly 711 are sandwiched between the back plate 705 and the frame708, which are mechanically coupled together to form a frame assembly750. The door latch 703 is positioned so that a handle portion isaccessible from a front side of the door cowl 701. The frame assembly750 is mounted to the inside of the door cowl 701 so that a latchportion of the door latch 703 protrudes through the frame assembly 750and the frame assembly 750 holds the door latch 703 in place. Thecassette receptacle 704 is pivotally mounted to the frame 708 using thedoor mounting bracket 710, the door pin 709, and the E-rings 722.Recessed bumpers 715 reduce strain on the door if the door is opened toofar or with excessive force. The torsion springs 724 and 725 aid theoperator in closing the door, as the door has considerable weight due tothe many components. The cassette orientation tab 799 prevents the doorfrom being closed if the pump cassette is oriented incorrectly in thecassette receptacle 704.

The bladder 707 is coupled to, and controlled by, a pneumatic circuit730 that provides positive and/or negative air pressure to the bladder707. Positive pressure supplied to the bladder 707 causes the bladder707 to expand in the direction of the frame 708. This, in turn, causesthe entire piston assembly 711 to move toward the control assembly 408,such that the piston cover 732 presses against the pump cassette 202and/or cassette receptacle 704, thereby producing an outward force onthe door 402 away from the control assembly 408. Alternatively,supplying negative pressure to the bladder 707 causes the pistonassembly 711 to move away from the pump cassette 202 and/or cassettereceptacle 704, thereby reducing the outward force on the door 402 awayfrom the control assembly 408.

The door assembly is designed to permit single-handed operation,specifically by pulling up on the handle. However, the door latch 703 isdesigned so that the door cannot be easily opened when the pump cassetteis in place in the cassette receptacle 704 with the door closed and thebladder of the piston assembly 711 is inflated. Specifically, the latchportions of the door latch 703 have undercuts that are engaged byrecesses in the front plate assembly 408. When the pump cassette is inplace in the cassette receptacle 704 with the door closed and the pistonassembly 711 is inflated so as to push the pump cassette against thebezel components of the front plate assembly 408, a sufficient force isgenerated between the door assembly 402 and the front plate assembly 408to prevent the door handle from being easily lifted. This door lockingmechanism is described in greater detail in Application D74.

FIG. 7B shows a front perspective view of the door assembly 402 inaccordance with an embodiment of the present invention. The humaninterface board assembly 712 having LEDs and the handle portion of thedoor latch 703 are visible from the front of the door cowl 701. Aportion of the cassette receptacle 704 and a portion of the pneumaticcircuit 730 are also visible.

FIG. 7C shows a rear perspective view of the door assembly 402 inaccordance with an embodiment of the present invention, in which thecassette receptacle 704 is in a retracted position. Visible at the rearof the door cowl 701 are the frame 708, the latch portion of the doorlatch 703, the cassette receptacle 704, the piston assembly 711, thedoor mounting bracket 710, the torsion springs 724 and 725, a portion ofthe human interface board assembly 712, and a portion of the pneumaticcircuit 730.

FIG. 7D shows a rear perspective view of the door assembly 402 inaccordance with an embodiment of the present invention, in which thecassette receptacle 704 is in an open position. Visible at the rear ofthe door cowl 701 are the frame 708, the latch portion of the door latch703, the cassette receptacle 704, the piston assembly 711, the doormounting bracket 710, the torsion springs 724 and 725, a portion of thehuman interface board assembly 712, and a portion of the pneumaticcircuit 730.

Occluder Assembly

The occluder assembly 404 is used to occlude various tubes as needed fortesting, compounding, and protection in the event of a failure. Theoccluder assembly 404 includes an occluder blade, an occluder spring, atwo-piece sheet metal enclosure, an occluder bladder, guide bushings,connectors, spacers, shafts, and miscellaneous hardware. The occluderassembly 404 for the compounder 102 includes a single occluder blade.The occluder assembly 404 includes a bladder that, when inflated,retracts the occluder, which enables fluid to pass through the tubing.In the event of a loss of pneumatics, the occluder assembly 404 defaultsto the occluded position so as to prevent fluid from passing through thetubing. The occluder assembly 404 is mounted to the front plate assembly408, and provides a mounting point for the vial spike assembly 406.

FIG. 8A shows a cross-sectional view of an occluder assembly 404 inaccordance with an embodiment of the present invention. Among otherthings, the occluder assembly 404 includes a housing 802, tubing 804connected to a bladder 808, a spacer 806 coupled to the front of thehousing 802, an occluder blade 814, an occluder spring 812, and anadjuster 810. The occluder spring 812 is essentially a flat spring. Theoccluder blade 814 is connected to the end of the occluder spring 812.When the bladder 808 is inflated, the occluder spring 812 is deflecteddownward at the middle so as to shorten the effective length of theoccluder spring 812 and retract the occluder blade 814. When the bladder808 is deflated, the occluder spring 812 extends flat and thereforeextends the occluder blade 814.

FIG. 8B shows a side perspective view of the occluder assembly 404 inaccordance with an embodiment of the present invention. The housing 802,the tubing 804, the occluder blade 814, and various standoffs 816 areshown.

FIG. 8C shows an exploded view of the occluder assembly 404 inaccordance with an embodiment of the present invention. The occluderassembly 404 includes an occluder blade 875, a shaft 874, a frontbracket 872, a rear bracket 871, a mylar sheet 869, a spring 868, ashaft spacer 867, an occluder bladder 866, slide blocks 865, 864, and861, four spike standoffs 863, a rear shaft 862, an enclosure bottom860, an enclosure top 859, double coated tape 858, three E-rings 852,and various hardware, 873, 857, 856, 855, 854, 853, and 851. Theoccluder blade 875 can be manually retracted if necessary. The edge ofthe occluder blade 875 that engages the tubing is typically rounded soas not to cut or crease the tubing.

Vial Spike Assembly

The vial spike assembly 406 is used to join the vial assembly 200 withthe spike receptacle 310 so as to cause spiking of the vial. The vialspike assembly 406 is preferably positioned so as to protrude throughthe top of the compounder 102. This provides easy access to the vialspike assembly 406 for inserting and removing the vial assembly 200 andspike receptacle 310 in support of compounding operations.

FIG. 9A shows an exemplary vial spike assembly 406 in accordance with anembodiment of the present invention. The vial spike assembly 406includes a cylinder 912 for receiving the vial assembly 200 and thespike receptacle 310, a base 914 for supporting the cylinder 912, apiston 904 operating within the cylinder and connected to a bladderplate 906 by a shaft 920, a bladder 918 for controlling movement of thepiston 904 within the cylinder 912 by operating on the bladder plate906, three switches (sensors) for sensing the presence and position ofthe vial assembly 200 and spike receptacle 310 (one of which is shown asswitch 908, and the other two located within the cylinder 912 and shownin later figures), a sensor cover 902, a spike cover 910 acting as alocking mechanism and including switch 908 that is operated by thesensor feature 346 of the spike receptacle 310, a drain port 916, andassociated plumbing and mounting hardware (not shown).

In order to perform spiking to allow for dilution of the anti-pathogencompound, the vial assembly 200 is first inserted into the cylinder 912.Sensors in the cylinder 912 detect the presence of the vial assembly 200within the cylinder 912 and also the position of the vial assembly 200within the cylinder 912.

Once the vial assembly 200 is in place within the cylinder 912, thespike receptacle 310 is inserted into the cylinder 912. As the spikereceptacle 310 is installed in the cylinder 912, the fit between thespike receptacle housing 344 and the inner wall of the cylinder 912causes the release tabs 358 on the spike guard 360 to move inward so asto release the guard 360. This enables the guard 360 to move easily. Thespike cover 910 is then closed. The switch 908 in the cover 910 isengaged by the sensor feature 346 of the spike receptacle 310 and sodetects the presence of the spike receptacle 310 and also closure of thecover 910.

FIG. 9B is a schematic diagram showing the vial spike assembly 406prepared for insertion of the vial assembly 200 and the spike receptacle310 in accordance with an embodiment of the present invention. Thecylinder 912 and cover 910 are shown, with the cover 910 in an openposition so that the vial assembly 200 and spike receptacle 310 can beinserted into the cylinder 912. The spike receptacle 310 includesorientation tabs 399 that align with orientation slots 922 in thecylinder 912.

FIG. 9C is a schematic diagram showing the vial spike assembly 406 withthe vial assembly 200 and spike receptacle 310 inserted into thecylinder 912 and the cover 910 in an open position in accordance with anembodiment of the present invention. In this configuration, the sensorsin the cylinder will detect the presence of the vial assembly 200 withinthe cylinder 912 and will also detect that the vial assembly 200 is in apre-spiking position within the cylinder 912. The switch 908 will notdetect presence of the spike receptacle 310 within the cylinder 912, asthe cover 910 is in the open position.

FIG. 9D is a schematic diagram showing the vial spike assembly 406 withthe vial assembly 200 and spike receptacle 310 inserted into thecylinder 912 and the cover 910 in a closed position in accordance withan embodiment of the present invention. In this configuration, theswitch 908 will indicate presence of the spike receptacle 310 within thecylinder 912 and closure of the cover 910.

FIG. 9E shows a cross-sectional view of the vial spike assembly 406 withthe vial assembly 200 and spike receptacle 310 locked and loaded andready for spiking, in accordance with an embodiment of the presentinvention. The vial receptacle 206 carrying the vial 210 with vial cap208 and vial septum 202 is positioned within the cylinder such that avial loaded sensor 926 is actuated and a vial spiked sensor 924 is notactuated by the switch engagement features 214. The spike housing 344 islocked by cover 910 such that the spike guard 360 with grommet 356 isaligned with the vial cap 208. The bladder 918 is deflated so that thebladder plate 906, shaft 920, and piston 904 are retracted.

Once the vial assembly 200 and spike receptacle 310 are positioned andlocked in place, the bladder 918 can be inflated to cause the bladderplate 906 to push the shaft 920 and piston 904 upward. This forces thevial assembly 200 upward into the spike receptacle 310, causing spikingof the vial. The sensors in the cylinder 912 detect the movement of thevial assembly 200 and completion of the spiking operation. The sensorscan also detect incomplete spiking, for example, insufficient movementof the vial assembly 200, in which case an anomaly signal is typicallysent to the process controller 120.

FIG. 9F shows a cross-sectional view of the vial spike assembly 406after spiking is completed, in accordance with an embodiment of thepresent invention. The bladder 918 is inflated so that the bladder plate906, shaft 920, and piston 904 have pushed the vial receptacle 206carrying the vial 210 with vial cap 208 and vial septum 202 up and intothe spike housing 344, which is held in place by the cover 910. With thevial receptacle 206 in this position, the vial loaded sensor 926 is notactuated and the vial spiked sensor 924 is actuated by the switchengagement features 214. During the spiking operation, the spike guard360 with grommet 356 was also pushed upward along with the vialreceptacle 206, and the grommet 356 is pressed tightly against the vialcap 206 so as to provide a secondary seal for the spikes in case fluidwere to leak through the septum 202 around the spikes 354 duringpumping.

When the spiking operation is complete, the bladder 918 can be deflated.The vial assembly 200 and the spike receptacle 310 will be permanentlyconnected, specifically by the engagement of the spike receptacleengagement teeth 204 on the vial receptacle 206 with the vial receptaclelocking feature 348 of the spike receptacle 310. The vial assembly 200and spike receptacle 310 can be removed from the cylinder by pull on thetubing that connects to the spike receptacle 310. As discussed above,the tubing is strongly attached to the spike receptacle 310 and so willnot disengage from the spike receptacle 310.

FIG. 10 shows an exploded view of the vial spike assembly 406 inaccordance with an embodiment of the present invention. Among otherthings, the vial spike assembly 406 includes a cylinder base 1001, aspike cylinder 912, a piston 904, a shaft 920, a bladder plate 906, aspike cover guide 1008, a spike cylinder base 1010, a bladder 918, acover bracket 1012, a spike cover 910, an ultra-subminiature snap-actionswitch 908, a plate 1017, a sensor cover 1018, a plunger 1020, twosnap-action enclosed switches 924 and 926, a dual sensor bracket 1022, asensor channel 902, and assorted hardware (not numbered). The piston 904is connected to the shaft 920 and is positioned within the spikecylinder 912. The cylinder base 1001 is attached to the bottom of thespike cylinder 912 and to the spike cylinder base 1010. The shaft 920extends through the cylinder base 1001 and the spike cylinder base 1010and is attached to the bladder plate 906, which in turn is attached tothe bladder 918. The switches 924 and 926 are attached to the dualsensor bracket 1022 and are positioned within corresponding openings inthe side of the spike cylinder 912. The sensor channel 902, coverbracket 1012, and spike cover guide 1008 are attached to the spikecylinder 912, with the sensor channel 902 covering the dual sensorbracket 1022. The switch 908 is attached to the spike cover 910 usingthe plate 1017 and the sensor cover 1018. The spike cover 910 isrotatably coupled to the spike cover guide 1008.

It should be noted that the vial spike assembly 406 can be designed tocause spiking in different ways while remaining within the scope of thepresent invention. For example, in alternative embodiments of theinvention, the vial assembly 200 can be held stationary while the spikereceptacle 310 is pushed onto the vial assembly 200 so as to causespiking. Also, the orientation of the vial assembly 200 and the spikereceptacle 310 can be reversed, such that the vial is inverted and thespikes enter the vial from below.

FIG. 11 shows an exemplary spiking mechanism in which the vial isinverted and the spikes enter the vial from below, in accordance with analternative embodiment of the present invention. In this embodiment, thespikes are of different length, with the shorter spike 1102 acting asthe inlet spike and the longer spike 1104 acting as the outlet spike. Asbuffer solution is added to the vial through the inlet spike 1102, theanti-pathogen compound in the vial becomes partially diluted. When thevial fills with fluid past the hollow of the outlet spike 1104, thediluted solution flows out the outlet spike 1104 to the working solutioncontainer.

Chassis Components

The chassis components 414 include various mechanical hardwarecomponents that are not considered part of the other assemblies. Amongother things, the chassis components 414 include the DC air pump 511, achassis base, a door sensor (and cable), mounting foot grommets, skins(housing), and associated hardware and fasteners. The housing includes amounting point, on the back of the unit, for the manual piston bladder(door) vent 503.

Compounding

As discussed above, the compounder 102 and the blood pumps 104 operateunder control of the process controller 120. In exemplary embodiments ofthe present invention, introduction of the anti-pathogen compound intothe RBCC is performed in two stages, a first stage in which theanti-pathogen compound is mixed with buffer solution to a firstconcentration, and a second stage in which the working solution is mixedwith the RBCC to a second concentration. The two-stage process isdescribed in more detail in Application D72.

FIG. 12 shows a process flow diagram describing the compounding andblood treatment process in accordance with an embodiment of the presentinvention. Rectangular blocks indicate commands sent to the pump by theprocess controller 120. Rounded blocks indicate instructions sent to theoperator by the process control 120.

The process starts in block 1201. In block 1202, the process controllerinstructs the operator to load and scan a compounder disposable set.After the compounder disposable set is loaded into the compounder, theprocess controller instructs the compounder to run a dry cassetteintegrity test (CIT) in block 1203. The compounder dry CIT is describedin more detail with reference to FIG. 14 below. Assuming the dry CIT isacceptable, the process controller instructs the operator to hang, scan,and connect the buffer solution bag so that the buffer solution bag isconnected to the inlet port of the pump cassette, in block 1204. Theprocess controller then instructs the compounder to prime the compounderdisposable set, in block 1205. Compounder priming is described in moredetail with reference to FIG. 15 below. The process controller theninstructs the compounder to run a wet CIT, in block 1206. The compounderwet CIT is described in more detail below with reference to FIG. 16.Assuming the wet CIT is acceptable, the process controller theninstructs the operator to scan and load the vial assembly and spikereceptacle into the vial spike assembly, in block 1207. The processcontroller then instructs the compounder to spike the vial, in block1208. Once spiking is completed, the process controller instructs thecompounder to perform the compounding operation, in block 1209.

As discussed above, compounding involves drawing buffer solution fromthe buffer solution container and pumping the buffer solution to thevial to dilute the anti-pathogen compound and pump the working solutionto the working solution container. The compounder measures the volume ofbuffer solution pumped to the vial so that the resulting workingsolution will have a predetermined concentration of anti-pathogencompound, within predetermined limits. After compounding is complete,the vial will contain some amount of fluid including buffer solution andperhaps a very small amount of anti-pathogen compound.

After compounding is complete, the process controller coordinates“teardown” of the compounder for removal and disposal of the compounderdisposable set from the compounder. Specifically, with reference againto FIG. 12, the process controller instructs the operator to heat sealthe working solution line, in block 1235, and then agitate and invertthe working solution bag, in block 1214. The process controller theninstructs the operator to heat seal the buffer solution line, in block1227. The process controller then instructs the operator to clamp thelines leading to the vial, in block 1228. The process controller theninstructs the compounder to release the compounder door, in block 1231,which is accomplished by deflating the bladder in the door assembly. Theprocess controller then instructs the compounder to release the bladderpressure on the vial spike (piston), in block 1232. The processcontroller then instructs the operator to remove the compounderdisposables from the compounder 1233.

After compounder “teardown” is complete, the process controllercoordinates the blood processing operations in which the RBCC is mixedwith working solution by the blood pumps 104 in order to produce theincubation solutions. Specifically, the process controller instructs theoperator to load and scan a blood pump disposable set in a bank of bloodpumps, in block 1210, and runs a blood pump dry cassette integrity test(CIT), in block 1212. The process controller then instructs the operatorto connect the disposable set to the working solution line using thesterile dock, in block 1213, and to open the break-away closure on theworking solution line, in block 1215. The process controller then primesthe blood pumps with working solution, in block 1216, and runs a bloodpump wet CIT on each of the blood pumps, in block 1217. The processcontroller then instructs the operator to open the break-away closure oneach of the RBCC lines, in block 1219, and then operates each of theblood pumps to mix RBCC with working solution to produce incubationsolution, in block 1219. When blood processing is complete, the processcontroller instructs the operator to heat seal each of the incubationbag lines, in block 1220, and also to heat seal the working solutionline, in block 1221. The process controller then tests the heat seal onthe incubation bag lines, in block 1223, and then instructs each of theblood pumps to release the door (by deflating the door bladder), inblock 1224. The process controller then instructs the operator to removeeach of the incubation bags, in block 1225, and tear down the blooddisposable set, in block 1226. Blood processing operations are describedin greater detail in Application D71.

If there is enough working solution remaining for another bloodprocessing cycle, then the process may recycle to block 1210 tocoordinate blood processing operations for another bank of blood pumps.If and when the working solution has expired or there is not enoughworking solution remaining for another blood processing cycle, then theprocess controller typically instructs the operator to remove theworking solution bag, in block 1236. The process ends in block 1234.

FIGS. 13A-B show a process flow diagram showing additional details ofthe compounding process in accordance with an embodiment of the presentinvention. The process begins in block 1301. A determination is madewhether the process controller has been on for more than 48 hours, inblock 1302. If so, then the process controller is restarted, in block1303, which essentially ends this iteration of the process, in block1304. If the process controller has not been on for more than 48 hours,then the pump configuration is checked, in block 1305. If the pumpconfiguration is incorrect, then the process enters anomaly handling, inblock 1306. If the pump configuration is correct, then a check is madeas to whether the occluder is engaged, in block 1307. If the occluder isengaged, then the process controller instructs the compounder to unsealthe door, in block 1308. The operator is then instructed to load thecompounder cassette and hang the solution bags, in block 1309. When thedoor is confirmed to be closed, in block 1310, the process controllerinstructs the compounder to seal the door, in block 1311, which is doneby inflating the bladder in the door assembly. If door sealing fails,then the process enters anomaly handling, in block 1312. If the doorseals, then the process controller instructs the compounder to performthe dry CIT, in block 1313. If the dry CIT fails, then the processenters anomaly handling, in block 1314. If the dry CIT passes, then theprocess controller instructs the operator to connect the buffer solutionline, in block 1315, and then instructs the compounder to prime, inblock 1316. If priming fails, then the process enters anomaly handling,in block 1317. If priming is successful, then the process controllerinstructs the compounder to perform the wet CIT, in block 1318. If thewet CIT fails, then the process enters anomaly handling, in block 1319.If the wet CIT passes, then the process controller instructs theoperator to load and lock the vial assembly and spike receptacle intothe vial spike assembly, in block 1320. The process controller confirmsthat the vial assembly and spike receptacle are loaded and locked, inblock 1321. If the vial assembly and spike receptacle cannot be loadedand locked, then the process enters anomaly handling, in block 1322.Upon confirmation that the vial assembly and spike receptacle are loadedand locked, then the process controller instructs the compounder toperform the spiking operation, in block 1323. If spiking fails, then theprocess enters anomaly handling, in block 1324. If spiking issuccessful, then the process controller instructs the compounder toperform the compounding operation, in block 1325. If the compoundingoperation fails, then the process enters anomaly handling, in block1326. Upon successful completion of the compounding operation, theprocess controller instructs the operator to heat seal the buffersolution line, in block 1327, and perform other operations (such asclamping the lines leading to the spike receptacle). The processcontroller instructs the operator to invert the working solution bag, inblock 1328. The process ends in block 1329.

FIG. 14 shows a process flow diagram describing the compounder dry CITprocess in accordance with an embodiment of the present invention. Thedry CIT process begins in block 1401. The positive pneumatic system isfirst isolated from the cassette and a baseline leak rate for thepositive assembly is obtained, specifically by closing the occluder, inblock 1402, opening all fluid valves and vial spike valve and closingthe variable valves, in block 1403, measuring the positive tank leakrate, in block 1404, venting the vial spike bladder if the positive tankleak rate is less than a predetermined threshold, and generating anerror signal if the positive tank leak rate is greater than or equal tothe predetermined threshold, in block 1405.

Then, the negative pneumatic system is isolated from the cassette and abaseline leak rate for the negative assembly is obtained, specificallyby closing all fluid valves, in block 1407, measuring the positive tankleak rate, in block 1408, and generating an error signal if the negativetank leak rate is greater than or equal to a predetermined threshold, inblock 1409.

Then, the process tests the cassette sheeting of the valves outside ofthe volcano valves, specifically by opening the occluder, in block 1410,measuring the positive tank leak rate, in block 1411, and generating anerror signal if the positive tank leak rate is greater than or equal toa predetermined threshold, in block 1412.

Then, the process tests the cassette sheeting at the center of thevolcano valves, specifically by opening valves 1A1 and 2A1 and all fluidvalves, in block 1413, measuring the positive and negative tank leakrates, in block 1414, and generating an error signal if the positive ornegative tank leak rate is greater than or equal to a predeterminedthreshold, in block 1415.

Then, the process verifies calibration of the positive transducers,specifically by isolating the positive transducers and connecting thepositive transducers together, in block 1416, measuring the positivetank leak rate, in block 1417, generating an error signal if thepositive tank leak rate is greater than or equal to a predeterminedthreshold, in block 1418, determining whether all positive transducersagree to within a predetermined threshold, in block 1419, and generatingan error signal if the positive transducers do not agree to within apredetermined threshold, in block 1420.

Then, the process verifies calibration of the negative transducers,specifically by isolating the negative transducers and connecting thenegative transducers together, in block 1421, measuring the negativetank leak rate, in block 1422, generating an error signal if thenegative tank leak rate is greater than or equal to a predeterminedthreshold, in block 1423, determining whether all negative transducersagree to within a predetermined threshold, in block 1424, and generatingan error signal if the negative transducers do not agree to within apredetermined threshold, in block 1425.

Finally, the process tests integrity of the fluid valve leading to thevent filter, specifically by filling the chamber, in block 1426,pressurizing the chamber, in block 1427, measuring the chamber leakrate, in block 1428, and generating an error signal if the chamber leakrate is greater than or equal a predetermined threshold, in block 1429.The dry CIT process ends in block 1430.

FIG. 15 shows a process flow diagram describing the compounder buffersolution priming process in accordance with an embodiment of the presentinvention. The priming process begins in block 1501. The process firstputs the chambers to the buffer bag through prime valves, in block 1502,and attempts to draw buffer solution from the buffer bag, in block 1503.If there is no flow, then an error signal is generated, in block 1507.Assuming there is flow, the process then gets the chambers from thebuffer bag through buffer in valves, in block 1504, and attempts to drawbuffer solution from the buffer bag, in block 1505. If there is no flow,then an error signal is generated in block 1507. If there is flow, thenthe process puts the chambers to the buffer bag through prime valves, inblock 1506, and attempts to draw buffer solution from the buffer bag, inblock 1508. If there is no flow, then an error signal is generated, inblock 1507. If there is flow, then the process checks for air in thechamber, in block 1509. If there is no air in the chamber, then thepriming completes successfully in block 1525. If there is air in thechamber during this first pass, then this is considered an errorcondition, in block 1510, but the process recycles to block 1504 for asecond pass. If, during the second pass, air is still detected in thechamber in block 1509, then an error signal is generated, in block 1511.

FIG. 16 shows a process flow diagram describing the compounder wet CITprocess in accordance with an embodiment of the present invention. Thewet CIT process begins in block 1601, and involves three passes ofblocks 1602 through 1619. In each pass, the occluder is retracted, inblock 1602, and various measurements are performed on both chambers, inblock 1603. If the measurements are outside of a predetermined threshold(NO in block 1604), then an error signal is generated, in block 1605.Otherwise, a chamber filling operation is performed, in block 1606.During the first pass, both chambers are filled; during the second pass,only one chamber is filled; during the third pass, only the otherchamber is filled. After the chamber filling operation, variousmeasurements are performed on the chambers, in block 1607. If themeasurements are outside of a predetermined threshold (NO in block1608), then an error signal is generated, in block 1609. At this point,the occluder is left retracted during the first pass, but is closedduring the second and third passes, in blocks 1610 and 1611. Therequired fluid valves are then opened, in block 1612, tank pressure isapplied to the chambers for a predetermined amount of time, in block1613, and various measurements are performed on the chambers, in block1614. If the measurements are outside of a predetermined threshold (NOin block 1615), then an error signal is generated in block 1616.Otherwise, the process determines whether the volume displaced is withinsome threshold, in block 1617. If not, then an error signal isgenerated, in block 1618. After all three passes are complete, theoccluder is disengaged, in block 1620, and both chambers are purged tothe buffer solution bag, in block 1621. The process ends in block 1622.

Manual Teardown

During normal compounder teardown, the compounder receives commands fromthe process controller to release pressure against the pump door so thatthe door can be opened by the operator. The pressure against the doorcomes from both the door piston bladder and the tubing occluder. Whilethe door piston bladder is pressurized and the tubing occluder isengaged, it is virtually impossible for the operator to open the pumpdoor and remove the pump cassette. If communication between the processcontroller and the compounder is lost, then the operator will need torelieve this pressure manually in order to remove the cassette. Amongother things, this involves the operator pressing the manual doorrelease valve on the back of the pump to deflate the bladder in the doorassembly. The operator may also manually retract the occluders ifnecessary.

FIG. 17 shows a process flow diagram describing the process for manualcompounder teardown in accordance with an embodiment of the presentinvention. The process begins in block 1701. The operator is instructedto heat seal the buffer solution line and close the clamps on the linesleading to the spike receptacle, in block 1702. The operator thenpresses the manual door release valve on the back of the pump to deflatethe bladder in the door assembly, in block 1703. The operator thenmanually retracts the occulder if necessary to allow opening of thedoor, in block 1704. The operator then removes the compounderdisposables, in block 1705. A close-case file is created indicating thefailure, in block 1706. The process ends in block 1707.

Volumetric Calibration Check

The compounder is typically checked for calibration periodically toverify its ability to accurately measure volumes of pumped fluids. Inexemplary embodiments of the invention, this calibration check is doneby running test measurements with two different test cassettes havingdifferent but known chamber volumes.

FIG. 18 shows a process flow diagram describing the volumetriccalibration check process in accordance with an embodiment of thepresent invention. The process begins in block 1801. The operator isinstructed to scan a bar code on the compounder in block 1802 in orderto test the compounder. The operator is then instructed to load thefirst test cassette, in block 1803. Upon confirmation that the door isclosed, in block 1804, the door is sealed, in block 1805. If the doorfails to seal properly, then the process enters anomaly handling, inblock 1806. If the door seals properly, a dry CIT is run, in block 1807.If the dry CIT fails, then the process enters anomaly handling, in block1808. If the dry CIT passes, then a volume calibration test is run tomeasure the volume of the chambers, in block 1809. If the differencebetween the measured volume and the known volume of the first cassetteis greater than or equal to some predetermined threshold, then theprocess enters anomaly handling, in block 1810. Otherwise, the door isreleased, in block 1811, and the operator is instructed to load thesecond test cassette, in block 1812. Upon confirmation that the door isclosed, in block 1813, the door is sealed, in block 1814. If the doorfails to seal properly, then the process enters anomaly handling, inblock 1815. If the door seals properly, a dry CIT is run, in block 1816.If the dry CIT fails, then the process enters anomaly handling, in block1817. If the dry CIT passes, then a volume calibration test is run tomeasure the volume of the chambers, in block 1818. If the differencebetween the measured volume and the known volume of the second cassetteis greater than or equal to some predetermined threshold, then theprocess enters anomaly handling, in block 1819. Otherwise, a test passdetermination is made, in block 1820, and a report is printed, in block1821. The door is released, in block 1822, and the operator isinstructed to remove the second test cassette, in block 1823. Theprocess ends in block 1824.

It should be noted that the flow diagrams are used herein to demonstratevarious aspects of the invention, and should not be construed to limitthe present invention to any particular flow or implementation. In somecases, certain process steps can be omitted or performed in a differentorder than shown without changing the overall results or otherwisedeparting from the true scope of the invention.

The present invention may be embodied in other specific forms withoutdeparting from the true scope of the invention. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive.

1. A method for attaching tubing to one or more spikes of a spikingassembly, the method comprising: overmolding a spike holder over aportion of each of the spikes such that each spike maintains asubstantially fixed position within the spike holder and at least onebarb is formed proximate to each spike; and attaching a tube to eachspike, each tube installed over one of the barbs.
 2. A method accordingto claim 67, further comprising: capturing the tubing within a housing,wherein the housing includes at least one element for engaging thetubing about the barbs so as to secure the tubes within the housing.